Direct single- or near-single copy detection of viruses is an important challenge in human health. Applications include the need to monitor emerging viral threats (H5N1 influenza and the SARS virus, for example), and the importance of understanding the long-term implications of nearly undetectable reservoirs of infection following antiretroviral therapy for HIV. While considerable effort has been expended on the development of ultrasensitive detection methods, the need remains for new technologies that are exceptionally sensitive, label-free, physically robust, and inexpensive. We hypothesize that two-dimensional photonic bandgap (2DPBG) sensors can fulfill all of these requirements. We will test that hypothesis by completing the following three Aims. In Aim 1, we will develop and test a new method for nanoscale patterning of single chain antibodies, and will implement that method in single-target 2DPBG sensors for vaccinia. In Aim 2, we will extend this methodology to the production of dual-target sensors. Finally, we will integrate these novel biosensors with microfluidic channels and with features for sample filtration and/or preconcentration in Aim 3. PUBLIC HEALTH RELEVANCE: Current methods for detecting viruses with high sensitivity - down to the single viral particle level - are expensive and complex. We propose to develop and test a new class of optical biosensors based on silicon that will be able to detect viruses simply and rapidly, with single-particle sensitivity. These new sensors will have applications in the detection of HIV, and emerging viral pathogens such as H5N1 influenza and SARS, among others.